Dicker Martina, Maresch Daniel, Strasser Richard
a Department of Applied Genetics and Cell Biology , University of Natural Resources and Life Sciences , Vienna , Austria.
b Department of Chemistry , University of Natural Resources and Life Sciences , Vienna , Austria.
Bioengineered. 2016 Nov;7(6):484-489. doi: 10.1080/21655979.2016.1201251. Epub 2016 Jun 22.
IgA nephropathy (IgAN) is a common autoimmune disease that is characterized by formation and deposition of IgA1-containing immune complexes frequently leading to end-stage kidney disease. The IgA1 in these immune complexes carries aberrantly glycosylated O-glycans. In circulating IgA1 these galactose-deficient mucin-type O-glycans are bound by autoantibodies and thus, contribute to immune complex formation and pathogenesis. Even though the disease is associated with the overproduction of aberrant O-glycans on IgA1, specific structure-function-studies of mucin-type O-glycans are limited. Compared to other expression hosts, plants offer the opportunity for de novo synthesis of O-glycans on recombinant glycoproteins as they are lacking the mammalian O-glycosylation pathway. Recently, we demonstrated that Nicotiana benthamiana are suitable for the generation of distinct O-glycans on recombinant IgA1. Here, we expand our engineering repertoire by in planta generation of galactose-deficient and α2,6-sialylated O-glycans which are the prevailing glycans detected on IgA1 from patients with IgAN.
IgA肾病（IgAN）是一种常见的自身免疫性疾病，其特征是含有IgA1的免疫复合物形成和沉积，常导致终末期肾病。这些免疫复合物中的IgA1携带异常糖基化的O-聚糖。在循环的IgA1中，这些缺乏半乳糖的粘蛋白型O-聚糖被自身抗体结合，因此有助于免疫复合物的形成和发病机制。尽管该疾病与IgA1上异常O-聚糖的过度产生有关，但粘蛋白型O-聚糖的具体结构-功能研究有限。与其他表达宿主相比，植物为重组糖蛋白上的O-聚糖从头合成提供了机会，因为它们缺乏哺乳动物的O-糖基化途径。最近，我们证明本氏烟草适合在重组IgA1上产生不同的O-聚糖。在这里，我们通过在植物中产生缺乏半乳糖和α2,6-唾液酸化的O-聚糖来扩展我们的工程方法，这些聚糖是在IgAN患者的IgA1上检测到的主要聚糖。
